Association between consumption of sweeteners and endometrial cancer risk: a systematic review and meta-analysis of observational studies.

The purpose of this study is to further investigate the relationship between sweetener exposure and the risk of endometrial cancer (EC). Up until December 2022, a literature search in an electronic database was carried out utilizing PubMed, Web of Science, Ovid, and Scopus. The odds ratio (OR) and 95 % confidence interval (CI) were used to evaluate the results. Sweeteners were divided into nutritional sweeteners (generally refers to sugar, such as sucrose and glucose) and non-nutritional sweeteners (generally refers to artificial sweeteners, such saccharin and aspartame). Ten cohort studies and two case-control studies were eventually included. The study found that in 12 studies, compared with the non-exposed group, the incidence rate of EC in the sweetener exposed group was higher (OR = 1·15, 95 % CI = [1·07, 1·24]). Subgroup analysis showed that in 11 studies, the incidence rate of EC in the nutritional sweetener exposed group was higher than that in the non-exposed group (OR = 1·25, 95 % CI = [1·14, 1·38]). In 4 studies, there was no difference in the incidence rate of EC between individuals exposed to non-nutritional sweeteners and those who were not exposed to non-nutritional sweeteners (OR = 0·90, 95 % CI = [0·81, 1·01]). This study reported that the consumption of nutritional sweeteners may increase the risk of EC, whereas there was no significant relationship between the exposure of non-nutritional sweeteners and the incidence of EC. Based on the results of this study, it is recommended to reduce the intake of nutritional sweeteners, but it is uncertain whether use of on-nutritional sweeteners instead of nutritional sweetener.

Long-term aspartame and saccharin intakes are related to greater volumes of visceral, intermuscular, and subcutaneous adipose tissue: the CARDIA study.

BACKGROUND: Artificial sweetener (ArtSw) intakes have been previously associated with higher BMI in observational studies and may promote visceral and skeletal muscle adipose tissue (AT) accumulation. This study aimed to determine whether habitual, long-term ArtSw or diet beverage intakes are related to greater AT depot volumes and anthropometry-related outcomes. METHODS: A validated diet history questionnaire was administered at baseline, year 7, and year 20 examinations in 3088 men and women enrolled in the Coronary Artery Risk Development in Young Adults cohort (CARDIA), mean age of 25.2 years and mean BMI of 24.5 kg/m2 at baseline. Volumes of visceral (VAT), intermuscular (IMAT), and subcutaneous adipose tissue (SAT) were assessed by computed tomography at year 25. Linear regression evaluated associations of aspartame, saccharin, sucralose, total ArtSw, and diet beverage intakes with AT volumes, anthropometric measures, and 25-year change in anthropometry. Cox regression estimated associations of ArtSw with obesity incidence. Adjustments were made for demographic and lifestyle factors, total energy intake, and the 2015 healthy eating index. RESULTS: Total ArtSw, aspartame, saccharin, and diet beverage intakes were positively associated with VAT, SAT, and IMAT volumes (all ptrend ≤ 0.001), but no associations were observed for sucralose intake (all ptrend > 0.05). In addition, total ArtSw, saccharin, aspartame, and diet beverage intakes were associated with greater body mass index, body weight, waist circumference, and their increases over a 25-year period. Except for saccharin (ptrend = 0.13), ArtSw, including diet soda, was associated with greater risks of incident obesity over a median 17.5-year follow-up (all ptrend < 0.05). CONCLUSIONS: Results suggest that long-term intakes of aspartame, saccharin, or diet soda may increase AT deposition and risk of incident obesity independent of diet quality or caloric intake. Coupled with previous evidence, alternatives to national recommendations to replace added sugar with ArtSw should be considered since both may have health consequences.

Inhibitory Effects of Artificial Sweeteners on Bacterial Quorum Sensing.

Despite having been tagged as safe and beneficial, recent evidence remains inconclusive regarding the status of artificial sweeteners and their putative effects on gut microbiota. Gut microorganisms are essential for the normal metabolic functions of their host. These microorganisms communicate within their community and regulate group behaviors via a molecular system termed quorum sensing (QS). In the present study, we aimed to study the effects of artificial sweeteners on this bacterial communication system. Using biosensor assays, biophysical protein characterization methods, microscale thermophoresis, swarming motility assays, growth assays, as well as molecular docking, we show that aspartame, sucralose, and saccharin have significant inhibitory actions on the Gram-negative bacteria N-acyl homoserine lactone-based (AHL) communication system. Our studies indicate that these three artificial sweeteners are not bactericidal. Protein-ligand docking and interaction profiling, using LasR as a representative participating receptor for AHL, suggest that the artificial sweeteners bind to the ligand-binding pocket of the protein, possibly interfering with the proper housing of the native ligand and thus impeding protein folding. Our findings suggest that these artificial sweeteners may affect the balance of the gut microbial community via QS-inhibition. We, therefore, infer an effect of these artificial sweeteners on numerous molecular events that are at the core of intestinal microbial function, and by extension on the host metabolism.

Artificial sweeteners induce glucose intolerance by altering the gut microbiota.

Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage.

[Theoretical risk assessment for dietary exposure to sodium saccharin among residents in Nanjing City].

OBJECTIVE: To evaluate the potential risk of dietary exposure to sodium saccharin among residents in Nanjing City, and provide scientific evidence for safety surveillance and risk management in processed foods. METHODS: Based on the survey of dietary consumption of residents in Nanjing City, combining with the limits of sodium saccharin in processed foods(GB 2760-2014), using @Risk software to establish the cumulative dietary exposure in a probabilistic way, and compared with the acceptable daily intake(ADI) for risk assessment. RESULTS: The average exposure of sodium saccharin of residents was 0. 69 mg/kg, accounted for 13. 80% of ADI, while high exposure(P97. 5) was 5. 37 mg/kg, and accounted for 107. 36% of ADI. The exposure of sodium saccharin of residents in all age groups exceeded ADI were ranged from 20. 60% to 132. 80%. The intake of sodium saccharin exposure of high exposures(P97. 5) exceeded ADI was 132. 80% and 110. 75% in 18-49 years and 11-17 years people respectively. Cooked nuts, candied fruit and bean products were the main sources of sodium saccharin exposure compared with others. CONCLUSION: Dietary exposure assessment shows that the risk dietary exposure to sodium saccharin is generally safe. Residents who intake these processed foods higher should be paid more attention to reduce the level of sodium saccharin exposure.

Long-Term Saccharin Consumption and Increased Risk of Obesity, Diabetes, Hepatic Dysfunction, and Renal Impairment in Rats.

Background and objectives: This study evaluated the effect of chronic consumption of saccharin on important physiological and biochemical parameters in rats. Materials and Methods: Male Wistar rats were used in this study and were divided into four groups: A control group and three experimental groups (groups 1, 2, and 3) were treated with different doses of saccharin at 2.5, 5, and 10 mg/kg, respectively. Each experimental group received sodium saccharin once per day for 120 days while the control group was treated with distilled water only. In addition to the evaluation of body weight, blood samples [total protein, albumin, glucose, lipid profile, alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatinine, and uric acid] and urine (isoprostane) were collected in zero time, and after 60 and 120 days for biochemical evaluation. Liver (catalase activity) and brain (8-hydroxy-2'-deoxyguanosine, 8-OHdG) tissues were collected at time zero and after 120 days. Results: The data showed that saccharin at 5 mg/kg increased body weight of treated rats after 60 (59%) and 120 (67%) days of treatment. Increased concentration of serum glucose was observed after treatment with saccharin at 5 (75% and 62%) and 10 mg/kg (43% and 40%) following 60 and 120 days, respectively. The concentration of albumin decreased after treatment with saccharin at 2.5 (34% and 36%), 5 (39% and 34%), and 10 mg/kg (15% and 21%) after 60 and 120 days of treatment, respectively. The activity of LDH and uric acid increased proportionally with dosage levels and consumption period. There was an increased concentration of creatinine after treatment with saccharin at 2.5 (125% and 68%), 5 (114% and 45%), and 10 mg/kg (26% and 31%) following 60 and 120 days, respectively. Catalase activity and 8-OHdG increased by 51% and 49%, respectively, following 120 days of treatment with saccharin at 2.5 mg/kg. Elevation in the concentration of isoprostane was observed after treatment with saccharin at all doses. Conclusions: The administration of saccharin throughout the treatment period was correlated with impaired kidney and liver function. Both hyperglycemic and obesity-inducing side effects were observed. There was an increased oxidative status of the liver, as well as exposure to increased oxidative stress demonstrated through the increased levels of isoprostane, uric acid, 8-OHdG, and activity of catalase. Therefore, it is suggested that saccharin is unsafe to be included in the diet.

Measuring Artificial Sweeteners Toxicity Using a Bioluminescent Bacterial Panel.

Artificial sweeteners have become increasingly controversial due to their questionable influence on consumers' health. They are introduced in most foods and many consume this added ingredient without their knowledge. Currently, there is still no consensus regarding the health consequences of artificial sweeteners intake as they have not been fully investigated. Consumption of artificial sweeteners has been linked with adverse effects such as cancer, weight gain, metabolic disorders, type-2 diabetes and alteration of gut microbiota activity. Moreover, artificial sweeteners have been identified as emerging environmental pollutants, and can be found in receiving waters, i.e., surface waters, groundwater aquifers and drinking waters. In this study, the relative toxicity of six FDA-approved artificial sweeteners (aspartame, sucralose, saccharine, neotame, advantame and acesulfame potassium-k (ace-k)) and that of ten sport supplements containing these artificial sweeteners, were tested using genetically modified bioluminescent bacteria from E. coli. The bioluminescent bacteria, which luminesce when they detect toxicants, act as a sensing model representative of the complex microbial system. Both induced luminescent signals and bacterial growth were measured. Toxic effects were found when the bacteria were exposed to certain concentrations of the artificial sweeteners. In the bioluminescence activity assay, two toxicity response patterns were observed, namely, the induction and inhibition of the bioluminescent signal. An inhibition response pattern may be observed in the response of sucralose in all the tested strains: TV1061 (MLIC = 1 mg/mL), DPD2544 (MLIC = 50 mg/mL) and DPD2794 (MLIC = 100 mg/mL). It is also observed in neotame in the DPD2544 (MLIC = 2 mg/mL) strain. On the other hand, the induction response pattern may be observed in its response in saccharin in TV1061 (MLIndC = 5 mg/mL) and DPD2794 (MLIndC = 5 mg/mL) strains, aspartame in DPD2794 (MLIndC = 4 mg/mL) strain, and ace-k in DPD2794 (MLIndC = 10 mg/mL) strain. The results of this study may help in understanding the relative toxicity of artificial sweeteners on E. coli, a sensing model representative of the gut bacteria. Furthermore, the tested bioluminescent bacterial panel can potentially be used for detecting artificial sweeteners in the environment, using a specific mode-of-action pattern.

Artificial sweeteners and mixture of food additives cause to break oral tolerance and induce food allergy in murine oral tolerance model for food allergy.

BACKGROUND: Processed foods are part of daily life. Almost all processed foods contain food additives such as sweeteners, preservatives and colourants. From childhood, it is difficult to avoid consuming food additives. It is thought that oral tolerance for food antigens is acquired during early life. If tolerance fails, adverse immune responses to food proteins may occur. OBJECTIVE: We hypothesized that food additives prevent acquisition of oral tolerance and aimed to verify the safety of food additives. METHODS: We induced experimental oral tolerance in mice for ovalbumin (OVA), a food antigen, by previous oral treatment with OVA before sensitization with OVA injections. Food additives were administered at the induction of oral tolerance, and food allergy was induced by repeated administration of OVA. Symptoms of food allergy were defined as a change in body temperature and allergic diarrhoea. RESULTS: Saccharin sodium and a mixture of food additives inhibited acquisition of oral tolerance. Hypothermia and allergic diarrhoea with elevation of OVA-specific IgE were induced in the murine model of oral tolerance. Analyses of antigen-presenting cells in mesenteric lymph nodes showed that food additives affected their manner of migration. Additionally, food additives decreased the proportion of CD25hi regulatory T cells among CD4+ T cells in the mesenteric lymph nodes. CONCLUSIONS AND CLINICAL RELEVANCE: A large amount of food additives may prevent acquisition of oral tolerance. Intake of food additives in early life may increase the risk of food allergies.

Sweet taste of saccharin induces weight gain without increasing caloric intake, not related to insulin-resistance in Wistar rats.

In a previous study, we showed that saccharin can induce weight gain when compared with sucrose in Wistar rats despite similar total caloric intake. We now question whether it could be due to the sweet taste of saccharin per se. We also aimed to address if this weight gain is associated with insulin-resistance and to increases in gut peptides such as leptin and PYY in the fasting state. In a 14 week experiment, 16 male Wistar rats received either saccharin-sweetened yogurt or non-sweetened yogurt daily in addition to chow and water ad lib. We measured daily food intake and weight gain weekly. At the end of the experiment, we evaluated fasting leptin, glucose, insulin, PYY and determined insulin resistance through HOMA-IR. Cumulative weight gain and food intake were evaluated through linear mixed models. Results showed that saccharin induced greater weight gain when compared with non-sweetened control (p = 0.027) despite a similar total caloric intake. There were no differences in HOMA-IR, fasting leptin or PYY levels between groups. We conclude that saccharin sweet taste can induce mild weight gain in Wistar rats without increasing total caloric intake. This weight gain was not related with insulin-resistance nor changes in fasting leptin or PYY in Wistar rats.

Sweetening yoghurt with glucose, but not with saccharin, promotes weight gain and increased fat pad mass in rats.

The claim that non-nutritive sweeteners accelerate body weight gain by disrupting sweet-calorie associations was tested in two experiments using rats. The experiments were modelled on a key study from a series of experiments reporting greater body weight gain in rats fed yoghurt sweetened with saccharin than with glucose (Swithers & Davidson, 2008). Both of the current experiments likewise compared groups fed saccharin- or glucose-sweetened yoghurt in addition to chow and water, while Experiment 1 included a third group (Control) given unsweetened yoghurt. In Experiment 1, but not in Experiment 2, rats were initially exposed to both saccharin- and glucose-sweetened yoghurts to assess their relative palatability. We also tested whether the provision of an energy-dense sweet biscuit would augment any effects of saccharin on food intake and weight gain, as seemingly predicted by Swithers and Davidson (2008). In Experiment 1 there were no differences in body weight gain or fat pad mass between the Saccharin and Control group, whereas the Glucose group was the heaviest by the final 5 weeks and at cull had the largest fat pads. Greater acceptance of saccharin predicted more weight gain over the whole experiment. Consistent with past reports, fasting blood glucose and insulin measures did not differ between the Saccharin and Control groups, but suggested some impairment of insulin sensitivity in the Glucose group. Experiment 2 found similar effects of glucose on fat mass, but not on body weight gain. In summary, adding saccharin had no detectable effects on body-weight regulation, whereas the effects of glucose on fat pad mass were consistent with previous studies reporting more harmful effects of sugars compared to non-nutritive sweeteners.

Artificial sweeteners: safe or unsafe?

Artificial sweeteners or intense sweeteners are sugar substitutes that are used as an alternative to table sugar. They are many times sweeter than natural sugar and as they contain no calories, they may be used to control weight and obesity. Extensive scientific research has demonstrated the safety of the six low-calorie sweeteners currently approved for use in foods in the U.S. and Europe (stevia, acesulfame-K, aspartame, neotame, saccharin and sucralose), if taken in acceptable quantities daily. There is some ongoing debate over whether artificial sweetener usage poses a health threat .This review article aims to cover thehealth benefits, and risks, of consuming artificial sweeteners, and discusses natural sweeteners which can be used as alternatives.

Is there a promoting role for artificial sweeteners in the evolution of bladder cancer? A meta-analysis of current literature.

INTRODUCTION: Urinary bladder cancer is a frequent neoplasia in the urogenital system. Ageing and smoking are the two main risk factors, however, some chemical agents such as artificial sweeteners could act as initiators or promoters. EVIDENCE ACQUISITION: After identifying trends in scientific literature, we conducted a wide search in PubMed database and a meta-analysis was performed on extracted data to determine the role of artificial sweeteners in the development of urinary bladder cancer. EVIDENCE SYNTHESIS: Twenty-one full reports were enrolled from screening of PubMed database into final analysis involving 116,568 subjects in comparisons. Overall, 13,682 and 102,886 cases were identified for bladder cancer patients and healthy controls, respectively. Among artificial sweetener users, 12.5% was the incidence of bladder cancer. In the control group, 11.2% of cases suffered from urothelial carcinoma of the bladder. About 40.7% of the patients suffering from urinary neoplasms and 37.8% of the healthy cases were artificial sweetener users, respectively. There were only minor differences in overall descriptive data. The incidence of urinary bladder cancer among artificial sweetener users and control cases showed no risk difference (RD: 0.00, CI: -0.06 to 0.06). The frequency of artificial sweetener use among patients suffering from urinary bladder neoplasms and healthy subjects was compared which showed equal occurrences (OR: 0.96, CI: 0.79 to 1.17). CONCLUSIONS: According to our results, the carcinogenic risk of artificial sweeteners is not proven. Saccharin should not be kept as a promoter in urothelial malignant transformation.

No Association between Low-Calorie Sweetener (LCS) Use and Overall Cancer Risk in the Nationally Representative Database in the US: Analyses of NHANES 1988-2018 Data and 2019 Public-Use Linked Mortality Files.

Low-calorie sweeteners (LCS) serve to replace added sugars in beverages and foods. The present goal was to explore any potential links between LCS use and cancer risk using the nationally representative National Health and Nutrition Examination Surveys 1988-2018 linked to 2019 Public-Use Linked Mortality Files. Analyses were based on dietary intakes from 1988-1994 NHANES (n = 15,948) and 1999-2018 NHANES (n = 48,754) linked to mortality data. The 1988-1994 NHANES separated aspartame from saccharin consumption; later data did not. LCS consumers were more likely to be older, female, non-Hispanic White, and with higher education and incomes compared to nonconsumers. LCS consumers were less likely to smoke and had higher HEI-2015 scores indicating higher-quality diets. In the cross-sectional NHANES data, LCS use was associated with higher BMI and higher prevalence of obesity and diabetes. There was no indication that aspartame, saccharin, or all LCS had any impact on overall cancer mortality. By using nonconsumers as the reference group, the hazard ratio (95th confidence interval, CI) group trend for tertiles of LCS use for 1988-1994 for aspartame was 1.00 (0.89-1.12), for saccharin 0.96 (0.79-1.10), and for 1988-2018 for all LCS was 0.92 (0.88-1.101). The null group trend effects were seen for analyses stratified by age/gender. The present analyses confirm past US-based reports that LCS use was associated with higher socioeconomic status, lower prevalence of smoking, and generally higher-quality diets. No association with cancer mortality was observed.

Insights into the effect of artificial sweeteners on the structure, stability, and fibrillation of type I collagen.

Artificial sweeteners (AS) are widely used as sugar substitutes because natural sweetener (sugar) leads to a number of health issues, including diabetes, obesity, and tooth decay. Since natural sugar (sucrose), diabetes and skin are highly interlinked, and also sucrose is known to inhibit the fibrillation of collagen, the major protein of the skin, a study on the impact of AS on collagen is important and essential. Herein, we have studied the influence of commonly used AS such as Sucralose (SUC), Aspartame (APM), and Saccharin (SAC) on the structure, stability, and fibrillation of collagen using various spectroscopic methods. The circular dichroism and turbidity results suggest that the AS does not disrupt the triple helix structure and also the fibrillar property of collagen, respectively. The fibrillar morphology was sustained, although there was a trivial difference in the entanglement of fibrils in the presence of SAC, compared to native collagen fibrils. The thermal stability of collagen is maintained in the presence of AS. Fluorescence and STD-NMR results indicate that the interaction between AS and collagen was weak, which supports the intact structure, stability, and fibrillation property of collagen. The current study thus suggests that the chosen AS does not influence collagen properties.

Relative risks of saccharin and calorie ingestion.

The risk of a person getting cancer from ingesting saccharin is compared with the risk of ingesting additional calories which cause excess body weight. It is found that, for a person who is 10% overweight, the risk of ingesting one diet soft drink, which would cause a decrease in life expectancy of 9 seconds, is approximately equal to the risk of ingesting one additional kilocalorie; that is, if ingesting a diet drink inhibits ingestion of more than 1 kilocalorie, its benefits exceed its risks.

Saccharin metabolism and tumorigenicity.

Exposure of male Charles River CDI rats to a 5% saccharin diet in utero and throughout weaning, conditions associated with tumor induction, did not induce detectable metabolism (less than 0.4% of the oral dose) of tritiated saccharin in vivo. No metabolites (less than 0.06 microgram per kilogram per 24 hours) were detected in the urine of normal rats given a tracer dose. Pretreatment with 3-methylcholanthrene did not induce saccharin metabolism.

Metabolic and cognitive improvement from switching to saccharin or water following chronic consumption by female rats of 10% sucrose solution.

High consumption of sugar-sweetened beverages (SSBs) is a risk factor for weight gain and metabolic disease. Whether this risk is reduced by switching to 'diet' beverages containing low-calorie sweeteners (LCS) is controversial. Two experiments modeled whether a switch from SSB to LCS beverages produced positive outcomes on behavioral and metabolic measures. Both experiments consisted of a Stage 1, in which adult female rats received unrestricted access to 10% sucrose solution in addition to chow and water for 4 (Experiment 1) or 8 weeks (Experiment 2). In Stage 2 rats were switched to either saccharin (Suc-Sacch) or water (Suc-Water) or remained on 10% sucrose (Suc-Suc) for a further 4 (Experiment 1) or 7 weeks (Experiment 2). Experiment 2 contained a fourth group that was maintained on water throughout (Water-Water). In both experiments energy intake and weight gain in Stage 2 was reduced for Suc-Sacch and Suc-Water groups relative to the Suc-Suc groups and at cull the Suc-Suc groups showed poorer insulin sensitivity and greater g/kg fat than Suc-Water and Suc-Sacch groups. In Experiment 2 short-term place recognition memory was impaired at the end of Stage 1 but recovered to a similar extent in the Suc-Water and Suc-Sacch groups; when the latter groups were compared with the Water-Water group, recovery was found to be essentially complete. A higher saccharin concentration in Experiment 2 than in Experiment 1 increased absolute amounts of saccharin ingested but intake solution volumes remained low. These results show that switching from sucrose to either water or saccharin produces equivalent improvements on both metabolic and cognitive measures.